2-Aminomethyl-1,4-benzodioxane derivatives, especially optically active compounds thereof are expected as a useful intermediate of preparing various medicines such as therapeutic agents for diseases of central nervous system (e.g., depression, anxiety, schizophrenia).
In general in regard to optically active medicines or intermediates thereof are required highly chemical purity and highly optical purity thereof. Therefore, it is an important problem to prepare optically active 2-aminomethyl-1,4-benzodioxane derivatives with highly chemical purity and highly optical purity.
Among the processes for preparing an 2-aminomethyl-1,4-benzodioxane derivative which have been developed, processes comparatively related to the process of the present invention are as follows:    (1) After 5-halo-2-hydroxybenzaldehyde and glycidyl tosylate are reacted in a base, 7-halo-2-hydroxymethyl-1,4-benzodioxane is obtained by oxidizing the formyl group of the reacted compound and then after tosylating it, an 2-aminomethyl-1,4-benzodioxane derivative is obtained by nucleophilic substitution with an amine derivative (WO 97/003071, Alan M. BIRCH, et al., J. Med. Chem., Vol. 42, No. 17, page 3342-3355 (1999)) and    (2) By three-steps reaction starting from 2-benzyloxyphenol and epichlorohydrin or glycidyl tosylate in sodium hydroxide, 2-hydroxymethyl-1,4-benzodioxane is obtained and then further by chlorination, by nucleophilic substitution reaction of phthalimide and by degradation of the imido portion, an 2-aminomethyl-1,4-benzodioxane derivative is obtained (Japanese patent publication A 6-9613).
In case of the above method (1), as the formyl group is oxidative-degraded, an expensive oxidation agent (m-chloroperbenzoic acid) must be much used and its reaction is dangerous. On the other hand, in case of the above method (2), the yield is low and not satisfactory. Therefore, these methods (1) and (2) have problems as a preparation of it for industrial scale.